Longstanding disease-free survival in idiopathic REM sleep behavior disorder: Is neurodegeneration inevitable?

INTRODUCTION: Studies estimate that >80% of patients with idiopathic REM sleep behavior disorder (iRBD) eventually develop parkinsonism or dementia. However, a small group remains disease-free for long periods, raising the question of whether they truly have prodromal disease. METHODS: We selected subjects with iRBD who were diagnosed at least 10 years previously, and were still disease free (longstanding iRBD) (n = 11). We compared them to 'early converters' (n = 27) defined as those who phenoconverted to parkinsonism or dementia within 4 years after diagnosis, and to age- and sex-matched healthy controls (n = 68). We compared the frequency and progression of numerous markers of prodromal synucleinopathy between groups, and assessed likelihood of meeting prodromal Parkinson's disease criteria. RESULTS: After at least 10 years follow-up, almost all longstanding iRBD subjects showed multiple features of neurodegeneration, and 9/11 met criteria for prodromal PD. Evolution of markers was slower than early-converters, with an annual increase in prodromal PD probability of 3.9 ±â€¯3.2% in longstanding iRBD compared to 12.4 ±â€¯7.8% for early-convertors (p-value = 0.002). However, subjects with longstanding iRBD at their last visit had similar prodromal measures as the baseline evaluation of the early-convertors, with similarly-abnormal UPDRS scores, quantitative motor tests, cognition and autonomic symptoms and signs. CONCLUSION: Although phenoconversion rates can differ dramatically between patients, almost all individuals with iRBD in our cohort appear to have underlying neurodegeneration.

Office-Based Screening for Dementia in Parkinson Disease: The Montreal Parkinson Risk of Dementia Scale in 4 Longitudinal Cohorts.

Importance: Parkinson disease dementia dramatically increases mortality rates, patient expenditures, hospitalization risk, and caregiver burden. Currently, predicting Parkinson disease dementia risk is difficult, particularly in an office-based setting, without extensive biomarker testing. Objective: To appraise the predictive validity of the Montreal Parkinson Risk of Dementia Scale, an office-based screening tool consisting of 8 items that are simply assessed. Design, Setting, and Participants: This multicenter study (Montreal, Canada; Tottori, Japan; and Parkinson Progression Markers Initiative sites) used 4 diverse Parkinson disease cohorts with a prospective 4.4-year follow-up. A total of 717 patients with Parkinson disease were recruited between May 2005 and June 2016. Of these, 607 were dementia-free at baseline and followed-up for 1 year or more and so were included. The association of individual baseline scale variables with eventual dementia risk was calculated. Participants were then randomly split into cohorts to investigate weighting and determine the scale's optimal cutoff point. Receiver operating characteristic curves were calculated and correlations with selected biomarkers were investigated. Main Outcomes and Measures: Dementia, as defined by Movement Disorder Society level I criteria. Results: Of the 607 patients (mean [SD] age, 63.4 [10.1]; 376 men [62%]), 70 (11.5%) converted to dementia. All 8 items of the Montreal Parkinson Risk of Dementia Scale independently predicted dementia development at the 5% significance level. The annual conversion rate to dementia in the high-risk group (score, >5) was 14.9% compared with 5.8% in the intermediate group (score, 4-5) and 0.6% in the low-risk group (score, 0-3). The weighting procedure conferred no significant advantage. Overall predictive validity by the area under the receiver operating characteristic curve was 0.877 (95% CI, 0.829-0.924) across all cohorts. A cutoff of 4 or greater yielded a sensitivity of 77.1% (95% CI, 65.6-86.3) and a specificity of 87.2% (95% CI, 84.1-89.9), with a positive predictive value (as of 4.4 years) of 43.90% (95% CI, 37.76-50.24) and a negative predictive value of 96.70% (95% CI, 95.01-97.85). Positive and negative likelihood ratios were 5.94 (95% CI, 4.08-8.65) and 0.26 (95% CI, 0.17-0.40), respectively. Scale results correlated with markers of Alzheimer pathology and neuropsychological test results. Conclusions and Relevance: Despite its simplicity, the Montreal Parkinson Risk of Dementia Scale demonstrated predictive validity equal or greater to previously described algorithms using biomarker assessments. Future studies using head-to-head comparisons or refinement of weighting would be of interest.